2.79J/3.96J/BEH.441J/HST522J Biomaterials-Tissue Interactions CONTENTS Introduction. Chapter 1. Irreversible Healing of Extracellular Matrix. Chapter 2. Cell-Matrix Interactions. Chapter 3. Synthesis of Tissues and Organs. TEXT: I. V. Yannas. Tissue and Organ Regeneration in Adults. New York: Springer, 2001. 1 Introduction. How are biomaterials used? Brief survey: from organs to cells. 2 How are biomaterials used? Today’s brief survey: from organ to cell outline of survey 1. Five Therapies for the Missing Organ Examples of permanent implants Examples of regenerated organs 2. Tissue and organ regeneration viewed as as processes of chemical synthesis. 3. What is the mechanism of organ regeneration? 4. Cell-matrix interactions. 5. The unit cell process. 3 Five Therapies for the Missing Organ 1. Transplantation (e.g., kidney transplant, heart transplant, liver transplant) 2. Autografting (e.g., heart bypass, skin grafting). 3. Permanent implants (e.g., hip prosthesis, pacemaker, breast implant) 4. In vitro synthesis (e.g., epidermis) 5. In vivo synthesis or regeneration (e.g., skin, nerves, conjunctiva). Remarks: Biomaterials are used in therapies #3, 4 and 5. Tissue engineering includes therapies #4 and 5. 4 Therapy # 3 : Example of permanent implant Another example of permanent implant AbioCor? Implantable Replacement Heart (http://www.abiocor.com) 5 Two cases of massively burnt patients 1. Six-year-old boy burned massively was treated in upper abdomen with own skin (meshed autograft) and in lower abdomen with template. 2. Middle-aged man burned in industrial fire, lost skin in right side of face was treated with template. 6 Example of poor nerve regeneration undegraded template inside nerve chamber Image removed due to copyright considerations. Image re ved due to copyright considerations. Example of good nerve regeneration template inside nerve chamber degraded optimally Image removed due to copyright considerations. Image re ved due to copyright considerations. 7 Ammonia synthesis (F. Haber) 3H 2 + N 2 2NH 3 reactor reactants products NOTE: stoichiometry of chemical equation expresses conservation of mass (Lavoisier) T, P Reactants → Products 2. Tissue and Organ Regeneration viewed as as processes of chemical synthesis. 8 Apply chemical symbolism and terminology to organ regeneration ? Example of “reaction diagram”: KC + DRT → E?BM?RR?D ? Reactants: cells, regulators, matrices ? Reactors: in vitro cell culture; in vivo (anatomical site) ? Products: either scar or regenerated tissue (or intermediate cases) 9 3. What is the mechanism of organ regeneration? 1. Data: There is an antagonistic relation between contraction of a wounded site and regeneration at that site. 2. Theory of induced regeneration: Blocking of contraction process leads to regeneration. 3. Contraction is mediated by cell-matrix interactions. Templates block these interactions. 10 4. Cell-matrix interactions A typified cell 11 Cell membrane 12 13 Cell-matrix interaction through integrins replace w/ artist redraw 14 Live Cell Imaging Freyman et al., 2001 Images removed due to copyright considerations. See Freyman, T.M. et al. “Micromechanics of Fibroplast Contraction of a Collagen-GAG Matrix.” Experimental Cell Research 269: 140-153 (2001) r . et al. “Mi ontracti n of a 1 Modified cell force monitor Strain Gauges Use to study unit cell processes quantitatively See Freyman et al., 2001 Aluminum Base Plate Silicone Culture Medium Collagen Matrix Adjustable Height Post 2 5. The unit cell process ? Study cell function as if it comprises several distinct processes. ? Identify the critical unit cell process. ? Focus attention on controlling the critical process. 3 Conditions for gene expression 4 Classic data: Cell-matrix interaction affects cell shape See D. Gospodarowiez et al., Cancer Res. 38:4155 (1978). S.C.G. Tseng et al., J. Cell Biol. 97:803 (1983). 5 Definition of unit cell process Cell + Insoluble Regulator Product Soluble Regulator A Soluble Regulator B Control volume dV Unit cell process confined conceptually in a control volume dV 6 Regulator A Regulator B + (on) – (off) Protagonist Cell + Matrix Activities/Functions Mitosis Synthesis Exocytosis Endocytosis Migration Contraction Product + Regulator C –– Various unit cell processes Other Unit Cell Process Example: Collagen Synthesis Regulator A (e.g. PDGF, TGF) SynthesisFibroblast + Collagen Fiber Collagen + Regulator B + – Collagen Degradation (i.e. synthesis of enzyme-collagenase) 7 Properties of a unit cell process Working Paradigm: Unit Cell Process